Epidemiologic studies have repeatedly identified malnutrition as a risk factor for tuberculosis (TB), which is the leading bacterial cause of deaths worldwide. The biologic basis for this association, however, remains unclear. Recent work has uncovered a large array of signaling molecules lying at the intersection of metabolic and immune signaling, among which nuclear hormone receptors (NHRs) and the insulin receptor have emerged as 2 prototypic examples. Existing knowledge indicates that the physiologic functions of many NHRs overlap with known epidemiologic risk factors for TB and that diabetes, itself, predisposes to TB. Here, we assimilate these data and identify a potential mechanism that may help to explain the long-standing clinical association between TB and host metabolism. Together, these data emphasize the underused potential of interdisciplinary dialog in current TB research efforts.